Human immunodeficiency virus (HIV)-infected patients commonly have unintentional weight loss and low serum micronutrient levels that have been correlated with disease progression. However, the relationship among these nutritional parameters, direct effects of the virus on the intestinal immune system and intestinal dysfunction and the role of opportunistic infections in progressive weight loss are not clear. These issues are extremely difficult to address in persons infected with HIV because a large percentage of HIV/AIDS patients are already taking a variety of nutritional supplements in an uncontrolled manner and dietary intake varies greatly. Furthermore, the rapid evolution of antiretroviral therapy complicates obtaining answers to these questions. To obviate these problems and also to control for additional variable such as time since inoculation and differences in viral inocula, we propose to use the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. The organization of the program project involves three projects and four cores. One project will define the natural history of weight loss and micronutrient deficiency in SIV-infected macaques and conduct two interventions to try and alleviate wasting. The next project will examine direct effects of SIV infection on the intestinal immune system and intestinal function. Another project will determine the relationship between key gastrointestinal opportunists (C. parvum, E. bieneusi, and M. avium) and weight loss. Thus this program project represents a multi-disciplinary approach by a group of interactive, experienced investigators to examine the interplay between 1) nutrition, 2) direct effects of SIV infection, and 3) opportunistic infections of the gastrointestinal tract on the pathogenesis of wasting.